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Phase I Dose Escalation Study of Intravenously Administered S64315 in Combination With Orally Administered Venetoclax in Patients With Acute Myeloid Leukaemia.

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ClinicalTrials.gov Identifier: NCT03672695
Recruitment Status : Active, not recruiting
First Posted : September 14, 2018
Last Update Posted : September 20, 2019
Sponsor:
Collaborator:
ADIR, a Servier Group company
Information provided by (Responsible Party):
Servier

Tracking Information
First Submitted Date  ICMJE September 4, 2018
First Posted Date  ICMJE September 14, 2018
Last Update Posted Date September 20, 2019
Actual Study Start Date  ICMJE November 28, 2018
Estimated Primary Completion Date March 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 12, 2019)
  • Incidence of Dose Limiting Toxicity (DLTs) [ Time Frame: At the end of cycle 1 (each cycle is 21 or 28 days). ]
  • Incidence and severity of AEs [ Time Frame: Through study completion, an average of 6 months. ]
  • Incidence and severity of SAEs [ Time Frame: Through study completion, an average of 6 months. ]
  • Number of participants with dose interruptions "will be measured and reported in the Outcome Measure results data table. [ Time Frame: Through study completion, an average of 6 months. ]
  • Number of participants with dose reductions "will be measured and reported in the Outcome Measure results data table. [ Time Frame: Through study completion, an average of 6 months. ]
  • Dose intensity [ Time Frame: Through study completion, an average of 6 months. ]
Original Primary Outcome Measures  ICMJE
 (submitted: September 13, 2018)
  • Incidence of Dose Limiting Toxicity (DLTs) [ Time Frame: At the end of cycle 1 (each cycle is 21 or 28 days). ]
  • Incidence and severity of AEs [ Time Frame: Through study completion, an average of 6 months. ]
  • Incidence and severity of SAEs [ Time Frame: Through study completion, an average of 6 months. ]
  • Number of participants with dose interruptions "will be measurede and reported in the Outcome Measure results tada table. [ Time Frame: Through study completion, an average of 6 months. ]
  • Number of participants with dose reductions "will be measurede and reported in the Outcome Measure results tada table. [ Time Frame: Through study completion, an average of 6 months. ]
  • Dose intensity [ Time Frame: Through study completion, an average of 6 months. ]
Change History Complete list of historical versions of study NCT03672695 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 12, 2019)
  • Anti-leukemic activity [ Time Frame: Through study completion, an average of 6 months. ]
    Using blood, bone marrow aspirate and medullary biopsy if available according to ELN 2017 criteria
  • Pharmacokinetic profile of S64315 administered in combination with Venetoclax in plasma: Area Under the Curve (AUC) [ Time Frame: From Day 1 of cycle 1 to the end of cycle 2 (each cycle is 21 or 28 days). ]
  • Pharmacokinetic profile of S64315 administered in combination with Venetoclax in plasma: Concentration at the end of infusion (Cinf) [ Time Frame: From Day 1 of cycle 1 to the end of cycle 2 (each cycle is 21 or 28 days). ]
  • Pharmacokinetic profile of S64315 administered in combination with Venetoclax in plasma: terminal half-life (t½z) [ Time Frame: From Day 1 of cycle 1 to the end of cycle 2 (each cycle is 21 or 28 days). ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase I Dose Escalation Study of Intravenously Administered S64315 in Combination With Orally Administered Venetoclax in Patients With Acute Myeloid Leukaemia.
Official Title  ICMJE An International Phase Ib Multicentre Study to Characterize the Safety and Tolerability of Intravenously Administered S64315, a Selective Mcl-1 Inhibitor, in Combination With Orally Administered Venetoclax, a Selective Bcl-2 Inhibitor in Patients With Acute Myeloid Leukaemia (AML).
Brief Summary The purpose of this study is to determine the safety profile, tolerability and the Recommended Phase 2 Dose of the combination S64315 with venetoclax in patients with Acute Myeloid Leukaemia.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Acute Myeloid Leukaemia
Intervention  ICMJE Combination Product: S 64315 (also referred as MIK665) and venetoclax

The treatment combination period should start the day after the planned dose of venetoclax is reached. The initial schedule will be a 21-day cycle with a weekly regimen for S64315 and a daily regimen for venetoclax.

S64315 should be administered 2 to 4 hours after venetoclax intake, via IV infusion. The dose escalation will start at 50 mg once a week and doses up to 1000 mg once a week might be explored.

Venetoclax will be administered orally once a day. The dose escalation will start at 100 mg daily and doses up to 600 mg daily might be explored. Venetoclax must be taken with a meal (ideally during breakfast) in order to avoid reduced efficacy.

Study Arms  ICMJE Experimental: S64315 and venetoclax administered in combination
Intervention: Combination Product: S 64315 (also referred as MIK665) and venetoclax
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: September 19, 2019)
12
Original Estimated Enrollment  ICMJE
 (submitted: September 13, 2018)
40
Estimated Study Completion Date  ICMJE March 31, 2022
Estimated Primary Completion Date March 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or female aged ≥ 18 years;
  2. Patients with cytologically confirmed and documented de novo, secondary or therapy-related AML as defined by World Health Organization (WHO) 2016 classification (Arber, 2016), excluding acute promyelocytic leukaemia (APL, French-American British M3 classification):

    • With relapsed or refractory disease without established alternative therapy or
    • Secondary to MDS treated at least by hypomethylating agent and without established alternative therapy or
    • ≥ 65 years not previously treated for AML and who are not candidates for intensive chemotherapy nor candidates for established alternative therapy
  3. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  4. Able to comply with study procedures
  5. Adequate renal function within 7 days before the inclusion of the patient defined as:

    • Serum creatinine ≤ 1.5 x ULN (upper normal limit) or calculated creatinine clearance (determined by MDRD) > 50 mL/min/1.73m2

  6. Adequate hepatic function within 7 days before the inclusion of the patient defined as:

    • AST and ALT ≤ 3 x ULN
    • Total serum bilirubin level ≤ 1.5 x ULN, except for patients with known Gilbert's syndrome, who are excluded if total bilirubin > 3.0 x ULN or direct bilirubin > 1.5 x ULN

Exclusion Criteria:

  1. Participant already enrolled and treated in the study
  2. Pregnancy, breastfeeding or possibility of becoming pregnant during the study
  3. Participation in another interventional study requiring investigational treatment intake at the same time or within 2 weeks or at least 5 halflives (whichever is longer) prior to first dose of IMP (participation in non-interventional registries or epidemiological studies is allowed). In case of biologic agents with a long half life such as CART cells, immune checkpoint antibodies, bispecific antibodies a flat wash-out of 28 days will be acceptable
  4. Presence of ≥ CTCAE Grade 2 toxicity (except alopecia of any grade) due to prior cancer therapy, according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCICTCAE, version 4.03).
  5. Known carriers of HIV antibodies
  6. Known history of significant liver disease
  7. Uncontrolled hepatitis B or C infection
  8. Known active acute or chronic pancreatitis
  9. History of myocardial infarction (MI), unstable angina pectoris, coronary artery bypass graft (CABG) within 6 months prior to starting study treatment
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   France,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03672695
Other Study ID Numbers  ICMJE CL1-64315-002
2018-001809-88 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description:

Plan Description: Researchers can ask for a study protocol, patient-level and/or study-level clinical trial data including clinical study reports (CSRs).

They can ask all interventional clinical studies:

  • submitted for new medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
  • Where Servier or an affiliate are the Marketing Authorization Holders (MAH). The date of the first Marketing Authorization of the new medicine (or the new indication) in one of the EEA Member States will be considered within this scope.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: After Marketing Authorisation in EEA or US if the study is used for the approval.
Access Criteria: Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.
URL: http://clinicaltrials.servier.com/
Responsible Party Servier
Study Sponsor  ICMJE Servier
Collaborators  ICMJE ADIR, a Servier Group company
Investigators  ICMJE
Principal Investigator: Andrew WEI The Alfred Hospital, Melbourne, Victoria
PRS Account Servier
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP